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Title: Evolution of substrate specificity in a retained enzyme driven by gene loss

Abstract

The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence oftrpandhisgenes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Finally, our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.

Authors:
 [1];  [2];  [1];  [3];  [4];  [1];  [5];  [5];  [1];  [6];  [6];  [4];  [7];  [2]; ORCiD logo [1]
  1. Unidad de Genomica Avanzada (Langebio) Irapuato (Mexico). Evolution of Metabolic Diversity Lab.
  2. Argonne National Lab. (ANL), Argonne, IL (United States). Computing, Environment and Life Sciences Directorate; Univ. of Chicago, IL (United States). Computation Inst.
  3. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Biosciences Division; Argonne National Lab. (ANL), Argonne, IL (United States). Structural Biology Center, Biosciences Division
  4. Univ. of Texas Health Science Center, Houston, TX (United States)
  5. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Biosciences Division
  6. Cinvestav-IPN, Mexico City (Mexico)
  7. Argonne National Lab. (ANL), Argonne, IL (United States). Midwest Center for Structural Genomics, Biosciences Division; Univ. of Texas Health Science Center, Houston, TX (United States); Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); Consejo Nacional de Ciencia y Tecnologia (CONACYT); National Science Foundation (NSF); National Institutes of Health (NIH)
OSTI Identifier:
1352728
Alternate Identifier(s):
OSTI ID: 1352729; OSTI ID: 1393838
Grant/Contract Number:
AC02-06CH11357; 132376; 179290; GM094585; 1611952; DE017382
Resource Type:
Journal Article: Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Juárez-Vázquez, Ana Lilia, Edirisinghe, Janaka N., Verduzco-Castro, Ernesto A., Michalska, Karolina, Wu, Chenggang, Noda-García, Lianet, Babnigg, Gyorgy, Endres, Michael, Medina-Ruíz, Sofía, Santoyo-Flores, Julián, Carrillo-Tripp, Mauricio, Ton-That, Hung, Joachimiak, Andrzej, Henry, Christopher S., and Barona-Gómez, Francisco. Evolution of substrate specificity in a retained enzyme driven by gene loss. United States: N. p., 2017. Web. doi:10.7554/eLife.22679.
Juárez-Vázquez, Ana Lilia, Edirisinghe, Janaka N., Verduzco-Castro, Ernesto A., Michalska, Karolina, Wu, Chenggang, Noda-García, Lianet, Babnigg, Gyorgy, Endres, Michael, Medina-Ruíz, Sofía, Santoyo-Flores, Julián, Carrillo-Tripp, Mauricio, Ton-That, Hung, Joachimiak, Andrzej, Henry, Christopher S., & Barona-Gómez, Francisco. Evolution of substrate specificity in a retained enzyme driven by gene loss. United States. doi:10.7554/eLife.22679.
Juárez-Vázquez, Ana Lilia, Edirisinghe, Janaka N., Verduzco-Castro, Ernesto A., Michalska, Karolina, Wu, Chenggang, Noda-García, Lianet, Babnigg, Gyorgy, Endres, Michael, Medina-Ruíz, Sofía, Santoyo-Flores, Julián, Carrillo-Tripp, Mauricio, Ton-That, Hung, Joachimiak, Andrzej, Henry, Christopher S., and Barona-Gómez, Francisco. Fri . "Evolution of substrate specificity in a retained enzyme driven by gene loss". United States. doi:10.7554/eLife.22679.
@article{osti_1352728,
title = {Evolution of substrate specificity in a retained enzyme driven by gene loss},
author = {Juárez-Vázquez, Ana Lilia and Edirisinghe, Janaka N. and Verduzco-Castro, Ernesto A. and Michalska, Karolina and Wu, Chenggang and Noda-García, Lianet and Babnigg, Gyorgy and Endres, Michael and Medina-Ruíz, Sofía and Santoyo-Flores, Julián and Carrillo-Tripp, Mauricio and Ton-That, Hung and Joachimiak, Andrzej and Henry, Christopher S. and Barona-Gómez, Francisco},
abstractNote = {The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence oftrpandhisgenes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Finally, our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.},
doi = {10.7554/eLife.22679},
journal = {eLife},
number = ,
volume = 6,
place = {United States},
year = {Fri Mar 31 00:00:00 EDT 2017},
month = {Fri Mar 31 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.7554/eLife.22679

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  • The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yetmore » not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.« less
  • The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. Here, we apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We also observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to amore » monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. These results show how gene loss can drive the evolution of substrate specificity from retained enzymes.« less
  • The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence oftrpandhisgenes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficientmore » form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Finally, our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.« less
  • Pyridoxal 5{prime}-phosphate (PLP)-dependent basic amino acid decarboxylases from the {beta}/{alpha}-barrel-fold class (group IV) exist in most organisms and catalyze the decarboxylation of diverse substrates, essential for polyamine and lysine biosynthesis. Herein we describe the first x-ray structure determination of bacterial biosynthetic arginine decarboxylase (ADC) and carboxynorspermidine decarboxylase (CANSDC) to 2.3- and 2.0-{angstrom} resolution, solved as product complexes with agmatine and norspermidine. Despite low overall sequence identity, the monomeric and dimeric structures are similar to other enzymes in the family, with the active sites formed between the {beta}/{alpha}-barrel domain of one subunit and the {beta}-barrel of the other. ADC contains bothmore » a unique interdomain insertion (4-helical bundle) and a C-terminal extension (3-helical bundle) and it packs as a tetramer in the asymmetric unit with the insertions forming part of the dimer and tetramer interfaces. Analytical ultracentrifugation studies confirmed that the ADC solution structure is a tetramer. Specificity for different basic amino acids appears to arise primarily from changes in the position of, and amino acid replacements in, a helix in the {beta}-barrel domain we refer to as the 'specificity helix.' Additionally, in CANSDC a key acidic residue that interacts with the distal amino group of other substrates is replaced by Leu{sup 314}, which interacts with the aliphatic portion of norspermidine. Neither product, agmatine in ADC nor norspermidine in CANSDC, form a Schiff base to pyridoxal 5{prime}-phosphate, suggesting that the product complexes may promote product release by slowing the back reaction. These studies provide insight into the structural basis for the evolution of novel function within a common structural-fold.« less
  • Protein phosphorylation plays a crucial role in mitogenic signal transduction and regulation of cell growth and differentiation. Dual specificity protein phosphatase 23 (DUSP23) or VHZ mediates dephosphorylation of phospho-tyrosyl (pTyr) and phospho-seryl/threonyl (pSer/pThr) residues in specific proteins. In vitro, it can dephosphorylate p44ERK1 but not p54SAPK-{beta} and enhance activation of c-Jun N-terminal kinase (JNK) and p38. Human VHZ, the smallest of the catalytically active protein-tyrosine phosphatases (PTP) reported to date (150 residues), is a class I Cys-based PTP and bears the distinctive active site signature motif HCXXGXXRS(T). We present the crystal structure of VHZ determined at 1.93 angstrom resolution. Themore » polypeptide chain adopts the typical a{beta}a PTP fold, giving rise to a shallow active site cleft that supports dual phosphorylated substrate specificity. Within our crystals, the Thr-135-Tyr-136 from a symmetry-related molecule bind in the active site with a malate ion, where they mimic the phosphorylated TY motif of the MAPK activation loop in an enzyme-substrate/product complex. Analyses of intermolecular interactions between the enzyme and this pseudo substrate/product along with functional analysis of Phe-66, Leu-97, and Phe-99 residues provide insights into the mechanism of substrate binding and catalysis in VHZ.« less